18F-fluoride PET for Early Non-invasive Assessment of Cortical Bone Formation - Non-invasive Assessment of Cortical Bone Formation - Version 1

• Register: EUCTR
• Last refreshed on: 10 December 2018
• Main ID: EUCTR2009-016523-61-GB
• Date of registration: 09/11/2009
• Prospective Registration: Yes
• Primary sponsor: King’s College London
• Public title: 18F-fluoride PET for Early Non-invasive Assessment of Cortical Bone Formation - Non-invasive Assessment of Cortical Bone Formation - Version 1
• Scientific title: 18F-fluoride PET for Early Non-invasive Assessment of Cortical Bone Formation - Non-invasive Assessment of Cortical Bone Formation - Version 1
• Date of first enrolment: 07/12/2009
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016523-61
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: No treatment
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects will be eligible for entry into the study if they meet all the following inclusion criterion:
• Ambulatory postmenopausal* women.
• Aged 50 to 85 years inclusive.
• Free of severe or chronically disabling condition.
• Without language barrier, cooperative, expected to return for all follow-up visits and who give written informed consent before entering the study.
• Lumbar spine, femoral neck and/or total hip BMD between 1 and 2.5 standard deviations below the average bone mineral density for young healthy women (i.e. T-score =-1 to > -2.5) as determined from the manufacturer’s database.
• Normal or clinically insignificant abnormal laboratory values.
• Normocalcemia Serum Calcium =2.15 mmol/l and =2.55 mmol/l.
• Vitamin D 25-(OH) Serum level of =15 ng/ml (37.4 nmol/L)
• Otherwise in good health as determined by past medical history, physical examination, vital signs, standard laboratory tests and urinalysis at screening and the opinion of the investigator.
• Screening BMI must be >18.5 and =30 and subjects must weigh at least 50 kg.
• At Screening vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed after the subject has rested for at least three (3) minutes, and again if clinically indicated after three (3) minutes in standing position. Vital signs should be within the following ranges:
o Tympanic (ear) temperature between 35.5 – 37.5 °C
o Systolic blood pressure, 90 – 160 mm Hg
o Diastolic blood pressure, 50 – 90 mm HG
o Pulse rate, 55 – 90 bpm
When blood pressure and pulse will be taken again after 3 minutes standing, there shall be no more than a 20 mm Hg drop in systolic or 10 mm Hg drop in diastolic blood pressure and increase in heart rate (>20 bpm) associated with clinical manifestation of postural hypotension.
All blood pressure measurements at other time-points should be assessed with the subject seated, unless stated otherwise in the protocol design, and utilizing the same arm for each determination.
• Ability to lie still in a PET scanner for 70 minutes

Definitions:
* Postmenopausal status is defined as:
• no vaginal bleeding for at least 12-months prior to enrolment in women with an intact uterus or
• a hysterectomy and/or bilateral oophorectomy 12-months after a naturally occurring menopause or
• a hysterectomy and/or bilateral oophorectomy prior to menopause and at least 12-months prior to enrolment with postmenopausal status defined biochemically by oestradial <73 pmol/L and FSH > 30 IU/L (confirmed prior to dosing).
• In women >50 and <60 years of age, FSH level > 30 IU/l (confirmed prior to dosing)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects will be excluded from the study if they meet any of the following criteria:

• Current or recent (within 1 year of enrolment) metabolic bone disorders such as Paget’s disease of bone, Cushing’s Syndrome, acromegaly, osteogenesis imperfecta, renal osteodystrophy, osteomalacia, any secondary causes of osteoporosis and/or bone loss, or serious illness affecting normal bone homeostasis.
• Current or recent (within 1 year of enrolment) disease which affects bone metabolism, such as hypoparathyroidism, hyperparathyroidism, or hyperthyroidism.
• Subjects with a history of hypothyroidism not on stable replacement therapy with levothyroxine (defined as no change of dose for at least 6-months prior to enrolment)
• Subjects with skeletal malignancies or bone metastases
• Recent (within 6-months of enrolment) fracture at any skeletal site.
• Significant osteoarthritis of the lumbar spine and/or hip(s) precluding a satisfactory DXA or 18F-fluoride PET scan.
• History of carcinoma in the previous 5 years or currently suspected carcinoma, with the exception of excised superficial lesions such as basal cell carcinoma and squamous cell carcinoma of the skin.
• Current or recent (within 1 year of enrolment) inflammatory bowel disease or malabsorption syndrome.
• Pre-existing hypercalcaemia
• Unexplained elevations of alkaline phosphatase.
• Current or recent (within 2 years of enrolment) nephrolithiasis or urolithiasis.
• Clinically significant renal, pancreatic, hepatic or cardiovascular disease, diabetes requiring pharmacotherapy indicated by:
o Clinically significant abnormal liver function tests such as SGOT, SGPT, GGT, alkaline phosphatase, or serum bilirubin
o Clinically significantly abnormal creatinine or BUN values or abnormal urinary constituents (e.g. albuminuria)
o Evidence of urinary obstruction or difficulty in voiding at screening
• History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory tests conducted at screening.
• Current or recent treatment (within 1 year of enrolment) with androgens or other anabolic steroids.
• Current or recent (within 1 year of enrolment) treatment with oestrogens (with or without progestins) or selective oestrogen receptor modulators (SERMs)
• Current or recent (within 1 year of enrolment) treatment with systemic corticosteroids, or orally inhaled or nasally inhaled corticosteroids in doses > 400 µg/day beclomethasone/day or equivalent.
• Current or previous treatment with IV or oral bisphosphonates, strontium ranelate, fluorides, calcitonin, teriparatide or PTH 1-84, aluminium supplements.
• Patients with 25-(OH) Vitamin D levels less than 15 ng/mL (37.4 nmol/L) prior to randomization
• Treatment with vitamin D or calcium supplements started less than one month prior to screening visit.
• Current or recent (within 1 year of enrolment) treatment with anticonvulsants.
• Subjects with a positive Hepatitis B surface antigen (HBsAg) or hepatitis C test result or a history of immunodeficiency diseases, including a positive HIV test result.
• Hypersensitivity to teriparatide or to any of the excipients.
• Prior external beam or implant radiation therapy to the skeleton.
• Poor medical or psychiatric risk for treatment in the opinion of the investigator.
• Subjects with anorexia nervosa, suspected bulimia (by history or physical) or obvious malnutrition
• Subjects exhibiting or with a history of any of the following signs or symptoms

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Osteopenia Please note this is not a study to investigate the use of the IMP for the treatment of osteopenia but rather to validate a non-invasive imaging technique for measuring early changes in bone in response to therapy.
MedDRA version: 12 Level: LLT Classification code 10049088 Term: Osteopenia

Intervention(s)

Trade Name: Teriparatide (Forsteo)
Product Name: Teriparatide
Pharmaceutical Form: Injection*
INN or Proposed INN: recombinant human parathyroid hormone (1-34)
CAS Number: 52232-67-4
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 250-

Trade Name: Adcal-D3 chewable tablets

Product Name: Adcal-D3 Chewable tablets
Pharmaceutical Form: Chewable tablet
INN or Proposed INN: Calcium carbonate
CAS Number: 471-34-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1500-
INN or Proposed INN: Colecalciferol
CAS Number: 67-97-0
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 400-

Primary Outcome(s)

Main Objective: The aim of this study is to investigate if 18F-fluoride PET can be used to assess the direct effects of treatment on bone turnover at the hip.

The primary objective is to compare changes in bone turnover at the hip measured by 18F-fluoride PET in postmenopausal women treated with teriparatide and untreated controls.

Secondary Objective: To compare changes in bone turnover at the hip with changes at the lumbar spine in response to teriparatide treatment.

To compare changes in bone turnover at the spine and hip with changes in biochemical markers of bone turnover and changes in bone mineral density.

To examine test-retest variability of 18F-fluoride PET measurements at the hip.

Primary end point(s): The primary objective is to demonstrate a significant increase in the rate of bone formation, measured by 18F-fluoride PET, in the hip following 12-weeks of treatment with the anabolic agent teriparatide as compared to controls.

Secondary ID(s)

PJMR0062105

Secondary Sponsor(s)

Guy's & St Thomas NHS Trust